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Yunxiao Zhang,1 Wanpu Yan,2 Yanyun Chen,1 Zhiyi Fan,1 Jiheng Chen1 1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Anesthesiology, Peking University Cancer Hospital & Institute, Beijing, People’s Republic of China; 2Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), The First Department of Thoracic Surgery, Peking University Cancer Hospital & Institute, Beijing, People’s Republic of ChinaCorrespondence: Jiheng ChenKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Anesthesiology, Peking University Cancer Hospital & Institute, 52 Fucheng Street, Haidian District, Beijing, 100142, People’s Republic of ChinaTel +86 10 88196553Fax +86 10 88122437Email jihengchen@bjmu.edu.cnPurpose: To compare the efficacy of a lower dose background infusion of oxycodone for patient-controlled intravenous analgesia (PCIA) with the conventional dose, following intercostal nerve block, for the management of postoperative pain in patients undergoing thoracoscopic lobectomy for lung cancer.Patients and Methods: This was a prospective, single-center, randomized, parallel-group, double-blind, controlled clinical trial. In total, 155 patients scheduled for elective radical lobectomy via video-assisted thoracoscopy were recruited from December 2018 to July 2019, of whom 140 were ultimately included in the study population. Patients were randomized to receive either oxycodone 0.25 mg/h (low-dose group, n=70) or oxycodone 0.5 mg/h (control group, n=70) as a background infusion for PCIA, following ropivacaine intercostal nerve block, for postoperative pain management. The primary endpoints were rest and dynamic visual analogue scale (VAS) scores within 72 h of the operation. The secondary endpoints were patient satisfaction scores, consumption of postoperative analgesics, times of patient-controlled analgesia (PCA), and adverse events.Results: All 140 enrolled patients completed the study requirements and were included in the final analysis. The rest and dynamic VAS scores at 4 h, 24 h, 48 h, and 72 h postoperative were comparable between the low-dose group and the control group (P> 0.05). However, the low-dose group had statistically significantly higher patient satisfaction scores (P< 0.001) and lower postoperative analgesic consumption (P< 0.001) as well as lower incidence of nausea and vomiting (P< 0.05). The times of PCA was not statistically significantly different between the two groups, and no serious adverse events occurred in either group (P> 0.05).Conclusion: A low-dose background infusion of oxycodone for postoperative PCIA can achieve a comparable analgesic effect to the conventional dose after thoracoscopic lobectomy for lung cancer. Furthermore, the low-dose regimen was associated with reduced consumption of oxycodone and increased patient satisfaction.Keywords: oxycodone, postoperative analgesia, patient-controlled intravenous analgesia, radical resection of lung cancer

PD-(L)1 inhibitor could improve the survival of locally advanced esophageal cancer (ESCA) patients, but we cannot tailor the treatment to common biomarkers. WNT signaling activation was associated with primary resistance to immunotherapy. In this study, we used our two clinical cohorts (BJCH

Background Surgery is an important component in the treatment of esophageal cancer. For patients not eligible for R0 resection, defined as locally advanced unresectable esophageal cancer, a new approach is to transform the cancer into a resectable state by preoperative treatment. However, preoperative chemo/radiation is unsatisfactory. Therefore, the aim of this study was to assess the safety and efficacy of chemo/radiotherapy combined with a programmed cell death protein 1 (PD‐1) inhibitor in the preoperative transformation of unresectable esophageal cancer. Methods Patients were evaluated as having unresectable, locally advanced esophageal cancer at baseline and were re‐evaluated as possible R0 resection candidates after PD‐1 inhibitor treatment. Patient data were derived from the prospective database of Peking University Cancer Hospital Thoracic Surgery I. Preoperative chemotherapy plus PD‐1 inhibitor treatment was defined as “transformation treatment.” The objective response rate, operation rate (proportion of patients who underwent surgery), R0 rate, and treatment safety were analyzed retrospectively. Results A total of 36 patients were enrolled into the study, and 94.4% (34/36) completed the planned transformation treatment. The objective response rate was 71.4% (25/35), and 75% (27/36) of the patients who completed transformation treatment underwent surgery. For these surgical patients, 81.5% (22/27) obtained R0 resection, and 22.2% (6/22) had pathological complete response (pCR). During transformation treatment, 22.2% (8/36) patients had ≥ grade 3 complications. There were no reoperations or perioperative deaths. After surgery, 29.6% (8/27) had ≥ grade 3 complications. Conclusions Esophagectomy after immunotherapy is safe with acceptable complications. Compared with chemotherapy alone, chemotherapy combined with immunotherapy had a more favorable transformation effect for patients with unresectable esophageal cancer., Thirty‐six patients were enrolled. All patients received preoperative immunotherapy and 94.4% (34/36) completed the planned transformation treatment. The objective response rate was 71.4% (25/35), and 75% (27/36) of the patients who completed transformation treatment underwent surgery. For these surgical patients, 81.5% (22/27) obtained R0 resection, and 22.2% (6/22) had pathological complete response (pCR) as confirmed by postoperative pathological report.

This study evaluated adebrelimab (a PD-L1 antibody) plus nab-paclitaxel and carboplatin as perioperative treatment for resectable NSCLC.Eligible patients had resectable stage II-III NSCLCs without driver gene. Patients received neoadjuvant treatment with 3 cycles of intravenous adebrelimab (20 mg/kg on day 1), nab-paclitaxel (100 mg/mA total of 37 patients were enrolled and received planned neoadjuvant therapy. Thirty-four (91.9%) patients underwent surgery. As of data cutoff on Jan 25, 2022, 19 (51.4%, 95% CI 35.9-66.6) of the 37 patients achieved MPR per BIPR and 11 (29.7%, 95% CI 17.5-45.8) patients achieved pathological complete response. Twenty-six (70.3%, 95% CI 54.2-82.5) patients had an objective response per RECIST v1.1. The 12-month event-free survival (EFS) rate was 77.8% (95% CI 54.1-90.3). Twenty-nine (78.4%) patients had grade ≥3 treatment-related adverse events (AEs) and nine (24.3%) had treatment-related serious AEs. No treatment-related deaths occurred. Grade ≥3 surgery-related AEs within 30 or 90 days after surgery were both reported in 5 (14.7%) patients.Adebrelimab plus nab-paclitaxel and carboplatin as perioperative therapy led to a substantial proportion of MPR and high resectability, with manageable toxicities. Based on the phase 1b results, phase 3 trial was initiated.

Background Multimodal opioid‐sparing analgesia is a key component of an enhanced recovery pathway after surgery that aims to improve postoperative recovery. Transcutaneous electrical acupoint stimulation (TEAS) is assumed to alleviate pain and anxiety and to modify the autonomic nervous system. This study aimed to determine the efficacy of TEAS for sedation and postoperative analgesia in lung cancer patients undergoing thoracoscopic pulmonary resection. Methods A total of 80 patients were randomized into two groups: the TEAS group and the sham TEAS combined with general anesthesia group. Postoperative pain levels at six, 24, 48 hours, and one month after surgery were measured using the visual analogue scale (VAS). Bispectral index (BIS) score during the TEAS prior to anesthetic induction, Observer's Assessment of Alertness/Sedation (OAAS) score, sufentanil consumption during postoperative patient‐controlled intravenous analgesia (PCIA), number of total and effective attempts of PCIA pump use, and incidence of postoperative nausea and vomiting were recorded and analyzed statistically. Results Patients in the TEAS group had significantly lower VAS scores at six, 24, and 48 hours after surgery (P

Objective Fluoroscopy guidance is generally required for endobronchial ultrasonography with guide sheath (EBUS-GS) in peripheral pulmonary lesions (PPLs). Virtual bronchoscopic navigation (VBN) can guide the bronchoscope by creating virtual images of the bronchial route to the lesion. The diagnostic yield and safety profiles of VBN without fluoroscopy for PPLs have not been evaluated in inexperienced pulmonologist performing EBUS-GS. Methods Between January 2016 and June 2017, consecutive patients with PPLs referred for EBUS-GS at a single cancer center were enrolled. The diagnostic yield as well as safety profiles was retrospectively analyzed, and our preliminary experience was shared. Results A total of 109 patients with 109 lesions were included, 99 (90.8%) lesions were visible on EBUS imaging. According to the procedure time needed to locate the lesion on EBUS, 24.8% (27/109) were deemed technically difficult procedures; however, no significant relationships were identified between candidate parameters and technically difficult procedures. The overall diagnosis yield was 74.3% (81/109), and the diagnostic yield of malignancy was 83.7% (77/92). Lesions larger than 20 mm [odds ratio (OR), 2.758; 95% confidence interval (95% CI), 1.077-7.062; P=0.034] and probe of within type (OR, 3.174; 95% CI, 1.151-8.757, P=0.026) were independent factors leading to a better diagnostic yield in multivariate analysis. About 30 practice procedures were needed to achieve a stable diagnostic yield, and the proportion of technically difficult procedures decreased and stabilized after 70 practice procedures. Regarding complications, one patient (0.9%) had intraoperative hemorrhage (100 mL) which was managed under endoscopy. Conclusions VBN without fluoroscopy guidance is still useful and safe for PPLs diagnosis, especially for malignant diseases when performed by pulmonologist without previous experience of EBUS-GS. VBN may simplify the process of lesion positioning and further multi-center randomized studies are warranted.

Background DNA damage repair is an important mechanism of platinum resistance. HOXB7 is one member of HOX family genes, which are essential developmental regulators and frequently dysregulated in cancer. Recently, its relevance in chemotherapy resistance and DNA damage repair has also been addressed. However, little is known regarding the association between HOXB7 and chemotherapy resistance in esophageal squamous cell carcinoma (ESCC). Methods The association between HOXB7 expression detected by immunohistochemisty and tumor regression grade (TRG) and long-term survival was analyzed in 143 ESCC patients who underwent neoadjuvant chemotherapy. CCK8 assay was used to examine the effect of cisplatin in a panel of four ESCC cell lines. A stable cell strain with HOXB7 knockdown of KYSE150 and KYSE450 was established to explore the effect on cisplatin sensitivity. The interaction of HOXB7 with Ku70, Ku80 and DNA-PKcs was determined by GST-pull down, coimmunoprecipitation and immunofluorescent colocalization. Finally, we investigated whether disrupting HOXB7 function by a synthetic peptide HXR9 blocking the formation of HOXB7/PBX could enhance cisplatin sensitivity in vitro and in vivo. Results High expression of HOXB7 was associated with cisplatin resistance and worse chemotherapy efficacy. HOXB7 knockdown reinforced cisplatin sensitivity. It was identified that HOXB7 interacts with Ku70, Ku80 and DNA-PKcs. HOXB7 knockdown was related to the downregulation of Ku70, Ku80 and DNA-PKcs as well as arrested cell cycle in S phase. HOXB7 inhibition by HXR9 had a synergistic effect to improve cisplatin sensitivity. Conclusion HOXB7 may be a biomarker for the prediction of chemoresistance of ESCC and serves as a promising therapeutic target.

PURPOSE To assess the benefits of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors as neoadjuvant/adjuvant therapies in locally advanced EGFR mutation-positive non–small-cell lung cancer. PATIENTS AND METHODS This was a multicenter (17 centers in China), open-label, phase II, randomized controlled trial of erlotinib versus gemcitabine plus cisplatin (GC chemotherapy) as neoadjuvant/adjuvant therapy in patients with stage IIIA-N2 non–small-cell lung cancer with EGFR mutations in exon 19 or 21 (EMERGING). Patients received erlotinib 150 mg/d (neoadjuvant therapy, 42 days; adjuvant therapy, up to 12 months) or gemcitabine 1,250 mg/m2 plus cisplatin 75 mg/m2 (neoadjuvant therapy, two cycles; adjuvant therapy, up to two cycles). Assessments were performed at 6 weeks and every 3 months postsurgery. The primary end point was objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1; secondary end points were pathologic complete response, progression-free survival (PFS), overall survival, safety, and tolerability. RESULTS Of 386 patients screened, 72 were randomly assigned to treatment (intention-to-treat population), and 71 were included in the safety analysis (one patient withdrew before treatment). The ORR for neoadjuvant erlotinib versus GC chemotherapy was 54.1% versus 34.3% (odds ratio, 2.26; 95% CI, 0.87 to 5.84; P = .092). No pathologic complete response was identified in either arm. Three (9.7%) of 31 patients and zero of 23 patients in the erlotinib and GC chemotherapy arms, respectively, had a major pathologic response. Median PFS was significantly longer with erlotinib (21.5 months) versus GC chemotherapy (11.4 months; hazard ratio, 0.39; 95% CI, 0.23 to 0.67; P < .001). Observed adverse events reflected those most commonly seen with the two treatments. CONCLUSION The primary end point of ORR with 42 days of neoadjuvant erlotinib was not met, but the secondary end point PFS was significantly improved.

In routine practice, one lung ventilation (OLV) is initiated upon pleural opening. We conducted a randomized controlled trial to compare lung collapse after preemptive OLV versus conventional OLV in thoracoscopic surgery. A total of 67 patients were enrolled (34 with conventional OLV; 33 with preemptive OLV). Preemptive OLV was conducted by closing the DLT lumen to the non‐ventilated lung immediately upon assuming the lateral position with the distal port closed to the atmosphere until pleural opening (>6 minutes in all cases). Lung collapse was assessed at 1, 5, 10, 20, 30 and 40 minutes after pleural opening using a 10‐point rating scale (10: complete collapse). The primary end point was the duration from pleural opening to satisfactory lung collapse (score of 8). Secondary end points included PaO2 and hypoxemia. The duration from pleural opening to satisfactory lung collapse was shorter in the preemptive OLV group (9.1 ± 1.2 vs. 14.1 ± 4.7 minutes, P

BACKGROUND Esophageal squamous cell carcinoma (ESCC) is the predominant type of esophageal cancer and most clinically curable patients are diagnosed with locally advanced disease. While the efficacy of preoperative treatment is relatively clear and well characterized, the effect of postoperative treatment, especially postoperative chemotherapy, remains controversial, and its role in the treatment strategy is obscure. We conducted an updated meta-analysis to include recent developments. METHODS A comprehensive search in the PubMed, Embase, and Cochrane databases was performed to identify studies published from the inception of each database to February 2018. The overall survival (OS) and disease-free survival (DFS) rates of patients treated with and without postoperative chemotherapy were analyzed and compared. Hazard ratios (HRs) and 95% confidence intervals (CIs) were used to assess the associations between postoperative chemotherapy and patient survival. Potential publication bias was assessed using Egger's line regression test. RESULTS A total of nine studies, including three randomized controlled trials and six retrospective studies, were retrieved from the databases, comprising a total of 1684 cases. The results showed that postoperative chemotherapy could improve OS (HR 0.78, 95% CI 0.66-0.91; P = 0.002) and DFS (HR 0.72, 95% CI 0.6-0.86; P < 0.001). CONCLUSIONS The current meta-analysis supports postoperative chemotherapy as an independent favorable prognostic factor for ESCC, which could improve both OS and DFS.

Background The current study aimed to determine the oncological efficacy and surgical safety of multiple pulmonary resections (MPRs) after prior curative surgery for local regional recurrent or second primary lung cancers. Methods All cases of lung cancer included in our prospective database between January 2000 and July 2015 were retrospectively reviewed. The oncological efficacy endpoints for synchronous and metachronous MPR were five-year overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS) rates after the second surgery. The surgical safety endpoints were postoperative mortality and complications (Clavien-Dindo classification) within 30 days. Results In total, 67 MPR cases were identified. There were no significant differences in the five-year OS and DFS between the synchronous MPR group (n = 50) and the propensity score-matched solitary major pulmonary resection group (n = 250) (5-year OS 84.5% vs. 69.0%, log rank P = 0.112; DFS 64.4% vs. 58.0%, log rank P = 0.278). The five-year OS and PFS of the metachronous MPR group (n = 17) were significantly better than those in the non-surgical control group (n = 19) (5-year OS 94.1% vs. 50.7%, log rank P = 0.005; 5-year PFS 53.9% vs. 10.5%, log rank P = 0.020). No postoperative mortality or severe complications occurred in the MPR group. Conclusion The oncological efficacy of MPR is superior to the non-surgical approach for the management of local regional recurrent or second primary lung cancer, with comparable postoperative mortality and complications.

Analysis of circulating tumor DNA (ctDNA) is emerging as a powerful tool for guiding targeted therapy and monitoring tumor evolution in patients with non-small cell lung cancer (NSCLC), especially when representative tissue biopsies are not available. Here, we have compared the ability of four leading technology platforms to detect epidermal growth factor receptor (EGFR) mutations (L858R, exon 19 deletion, T790M and G719X) in ctDNA from NSCLC patients. Two amplification refractory mutation systems (cobas-ARMS and ADx-ARMS), a droplet digital polymerase chain reaction (ddPCR) and a next-generation sequencing (Firefly NGS) platform were included in the comparison. Fifteen EGFR mutations across twenty NSCLC patients were identified. Firefly NGS, cobas-ARMS and ddPCR all displayed superior sensitivity while ADx-ARMS was better suited for the qualitative detection of EGFR mutations with allele frequency higher than 1% in plasma and tissue samples. We observed high coincidence between the plasma and tissue EGFR mutational profiles for three driver mutations (L858R, exon 19 deletion and G719X) that are known targets of first generation EGFR-TKI therapies among patients who relapsed. Discrepancies between tissue and plasma EGFR mutational profiles were mainly attributable to spatial and temporal tumor heterogeneity, mutation inhibition due to therapy response and drug resistance (T790M). This study illustrates the challenges associated with selection of a technology platform for EGFR ctDNA analysis in the context of treatment evaluation and drug resistance detection.

To assess the benefits of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors as neoadjuvant/adjuvant therapies in locally advancedThis was a multicenter (17 centers in China), open-label, phase II, randomized controlled trial of erlotinib versus gemcitabine plus cisplatin (GC chemotherapy) as neoadjuvant/adjuvant therapy in patients with stage IIIA-N2 non-small-cell lung cancer withOf 386 patients screened, 72 were randomly assigned to treatment (intention-to-treat population), and 71 were included in the safety analysis (one patient withdrew before treatment). The ORR for neoadjuvant erlotinib versus GC chemotherapy was 54.1% versus 34.3% (odds ratio, 2.26; 95% CI, 0.87 to 5.84;The primary end point of ORR with 42 days of neoadjuvant erlotinib was not met, but the secondary end point PFS was significantly improved.

Background To determine oncologic and surgical outcomes after multiple pulmonary resections (MPR) for synchronous or metachronous lung cancer with multiple pulmonary sites of involvement and to identify prognostic factors for these patients. Methods We retrospectively analyzed data from two Chinese high-volume institutions. Eligible patients underwent MPR for synchronous or metachronous lung cancer with multiple pulmonary sites of involvement. Overall survival and disease-free survival after MPR were analyzed, and prognostic factors were explored using multivariable Cox analysis. Postoperative mortality and major morbidities within 30 days were evaluated. Results In total, 142 patients were included: 36 (25%) underwent MPR for the metachronous disease, and 106 (75%) underwent MPR for the synchronous disease. Five-year disease-free survival was 85.4% for the metachronous group and 69.1% for the synchronous group; 5-year overall survival was 86.1% and 84.8%, respectively. Five-year accumulated local and distant recurrence rates were 11.9% and 3.0% for the metachronous group and 26.6% and 5.9% for the synchronous group, respectively. In the synchronous MPR group, a larger sum of tumor size (hazard ratio [HR] 1.04; 95% confidence interval [CI], 1.00 to 1.08) and regional nodal involvement (HR 6.17; 95% CI, 1.42 to 35.46) were both independently associated with worse overall survival. In the metachronous MPR group, the longer disease-free interval was independently associated with favorable overall survival (HR 0.94; 95% CI, 0.88 to 0.98) and disease-free survival (HR 0.96; 95% CI, 0.93 to 0.99). There was no 30-day mortality. The overall rate of major morbidities was 12%. Conclusions Multiple pulmonary resection is valid for patients with synchronous and metachronous lung cancer with multiple pulmonary sites of involvement.

Background: The incidence of synchronous and metachronous multiple primary lung cancers (MPLCs) has been increasing recently. The new multidisciplinary classification of lung adenocarcinoma and TNM Classification of Lung Cancer (7 th edition, 2009), have improved the understanding of MPLC. Most researchers recommend that surgical therapy should be actively pursued if the patient’s physical condition and lung function permit it and if a complete cure can be achieved. However, few studies have reported the long-term efficacy of surgical treatment for MPLC, which we explored in this study. Methods: A total of 1,290 Lung cancer patients from a prospectively maintained database, treated by a single surgeon group between January 2000 and July 2013, at Beijing Cancer Hospital, Peking University, were reviewed. We retrospectively analyzed the clinical data of 31 patients diagnosed with MPLC out of 1290 lung cancer patients, focusing on long-term survival. Results: MPLC patients accounted for 2.4% (31/1,290) of the patient cohort: 27 had synchronous MPLC (87.1%) and 4 had metachronous MPLC (12.9%). The 1-, 3- and 5-year postoperative survival rates were 100%, 75.8% and 75.8%. On stratification according to TNM stage, the 1-, 3- and 5-year of patients with stage I cancer (20 patients) were 100%, 77.2% and 77.2%, not statistically significant with those for the entire cohort (1,290 patients; 95.4%, 80.5% and 66.2%, P=0.455). Conclusions: When the patient’s physical condition and tumor-related factors permit it, surgery should be the first choice of treatment for MPLC; it is associated with an equivalent efficacy to that of surgery for single primary lung cancer.

Background: Lung cancer is one of the most prevalent malignancies worldwide. The number of anatomic lung cancer resections performed via video-assisted thoracoscopic surgery (VATS) is growing rapidly. Staplers are widely used in VATS procedures, but there is limited clinical data regarding how they might affect performance and postoperative outcomes, including air leak. This clinical trial assessed the use of a powered stapler in VATS lung resection, with a primary study endpoint being occurrence and duration of air leak and prolonged air leak (PAL). Methods: Data was collected from a single arm, multi-center study in Chinese patients receiving VATS wedge resection or lobectomy. Intra-operative data included surgery duration; cartridge selection for ligation/transection of bronchus, major vessels, and lung parenchyma; staple line interventions; blood loss; and device usage. Post-operative data included air leak assessments, chest tube duration, length of hospital stay, and adverse events (AEs). Results: A total of 94 procedures across four institutions in China were included in the final analysis: 15 wedge resections, 74 lobectomies, and five wedge resections followed by lobectomies. Post-operative air leak occurred in five (5.3%) patients who had lobectomy procedures, with PAL in one (1.1%) patient. Sites were generally consistent relative to cartridge use by tissue type. The incidence of stapler firings requiring surgical interventions was seven out of 550 (1.3%). Surgeons participating in the study were satisfied with the articulation and overall usability of the stapler. Conclusions: The powered staplers make the VATS procedure easier for the surgeons and have achieved intra- and post-operative patient outcomes comparable to those previously reported.

// Lu-Yan Shen 1, * , Hui Wang 1, * , Bin Dong 2 , Wan-Pu Yan 1 , Yao Lin 1 , Qi Shi 1 , Ke-Neng Chen 1 1 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery I, Peking University Cancer Hospital and Institute, Beijing, People’s Republic of China 2 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology, Peking University Cancer Hospital and Institute, Beijing, People’s Republic of China * These authors contributed equally to this work Correspondence to: Ke-Neng Chen, e-mail: chenkeneng@bjmu.edu.cn Keywords: chemotherapy response, ESCC, neoadjuvant chemotherapy, gene expression profiling, MUC Received: August 27, 2015 Accepted: November 21, 2015 Published: December 10, 2015 ABSTRACT Background: Heterogeneous efficacy of neoadjuvant chemotherapy has led to controversies that have limited its application in clinical practice. Thus, we aimed to identify potential biomarkers predicting esophageal squamous cell carcinoma (ESCC) chemo-responsiveness by gene expression profiling. Methods: CCK8 assay was used to evaluate the growth inhibitory effect of different concentrations of cisplatin and paclitaxel on the ESCC cell lines EC109, KYSE450, KYSE410, KYSE510, and KYSE150 to differentiate between chemosensitive and chemoresistant cell lines. Gene expression profiling and Real-time PCR were applied to analyze and validate the gene expression differences between chemosensitive and chemoresistant cell lines. IHC was conducted to examine the expression of selected target markers MUC4, MUC13, and MUC20 in 186 ESCC resection samples and the relationships between their expression and tumor regression grade was analyzed. Moreover, RNAi was conducted to instantly block the expression of MUC4, MUC13, and MUC20 to observe their influences on chemo-responsiveness. Results: EC109 was found to be relatively sensitive to both cisplatin and paclitaxel, while KYSE410 was relatively resistant to cisplatin, KYSE510 was relatively resistant to paclitaxel. Gene expression profiling analysis showed that 2018 genes were differentially expressed in sensitive cell line compared to resistant cell lines. The expression patterns of MUC4, MUC13, MUC20 were validated. Low expression of MUC4 and MUC20 in resection samples was significantly correlated with better TRG. Blockage of MUC20 and MUC13 decreased the drug-resistance capacity and chemosensitivity, respectively. Conclusions: MUC4 and MUC20 were identified as potential biomarkers for predicting the efficacy of neoadjuvant chemotherapy in ESCC patients.

Objective Comparative survival between neoadjuvant chemotherapy and adjuvant chemotherapy for patients with cT2-4N0-1M0 non–small cell lung cancer has not been extensively studied. Methods Patients with cT2-4N0-1M0 non–small cell lung cancer who received platinum-based chemotherapy were retrospectively identified. Exclusion criteria included stage IV disease, induction radiotherapy, and targeted therapy. The primary end point was disease-free survival. Secondary end points were overall survival, chemotherapy tolerance, and ability of Response Evaluation Criteria In Solid Tumors response to predict survival. Survival was estimated using the Kaplan–Meier method, compared using the log-rank test and Cox proportional hazards models, and stratified using matched pairs after propensity score matching. Results In total, 330 patients met the inclusion criteria (n = 92/group after propensity-score matching; median follow-up, 42 months). Five-year disease-free survival was 49% (95% confidence interval, 39-61) for neoadjuvant chemotherapy versus 48% (95% confidence interval, 38-61) for adjuvant chemotherapy (P = .70). On multivariable analysis, disease-free survival was not associated with neoadjuvant chemotherapy or adjuvant chemotherapy (hazard ratio, 1.1; 95% confidence interval, 0.64-1.90; P = .737), nor was overall survival (hazard ratio, 1.21; 95% confidence interval, 0.63-2.30; P = .572). The neoadjuvant chemotherapy group was more likely to receive full doses and cycles of chemotherapy (P = .014/0.005) and had fewer grade 3 or greater toxicities (P = .001). Response Evaluation Criteria In Solid Tumors response to neoadjuvant chemotherapy was associated with disease-free survival (P = .035); 15% of patients receiving neoadjuvant chemotherapy (14/92) had a major pathologic response. Conclusions Timing of chemotherapy, before or after surgery, is not associated with an improvement in overall or disease-free survival among patients with cT2-4N0-1M0 non–small cell lung cancer who undergo complete surgical resection.

It remains unclear whether postoperative chemotherapy improves survival among patients with esophageal squamous cell carcinoma who have undergone preoperative chemotherapy and radical resection.Patients treated between January 2000 and December 2016 were reviewed. Eligible patients were divided into two groups: perioperative chemotherapy (preoperative and postoperative chemotherapy) and neoadjuvant chemotherapy only. The primary endpoint was disease-free survival; the secondary endpoints were overall survival and toxicities attributable to postoperative chemotherapy. To minimize the effect of patient heterogeneity between the two groups, we used propensity score matching. The survival analysis was performed using univariate analysis and a multivariable Cox regression model.In total, 252 patients were included in the study. Most were men (208 of 252; 82.5%); median age was 59 years. The follow-up rate was 93.3%. Age, performance status, minimally invasive surgery, and Clavien-Dindo classification were statistically different between the groups (P.05). After propensity score matching, each group had 59 patients. Five-year disease-free survival (52.4% vs 43.6%, P = .372) and overall survival (68.6% vs 62.4%, P = .359) were not statistically different between the neoadjuvant chemotherapy group and the perioperative chemotherapy group. Cox regression identified both pathologic nodal stage and tumor regression grade are independent prognostic factors for disease-free survival and overall survival (P .05); adjuvant chemotherapy did not influence disease-free survival (hazard ratio 1.049, 95% confidence interval, 0.587 to 1.876, P = .872) or overall survival (hazard ratio 1.297; 95% confidence interval, 0.606 to 2.775, P = .504). In the perioperative chemotherapy group, 8.5% of patients (5 of 59) had grade 3 or greater toxicity.Adjuvant chemotherapy is not indicated for patients with locally advanced esophageal squamous cell carcinoma after neoadjuvant platinum-based chemotherapy and surgery.

Background The current study aimed to determine the oncological efficacy and surgical safety of multiple pulmonary resections (MPRs) after prior curative surgery for local regional recurrent or second primary lung cancers. Methods All cases of lung cancer included in our prospective database between January 2000 and July 2015 were retrospectively reviewed. The oncological efficacy endpoints for synchronous and metachronous MPR were five‐year overall survival (OS), disease‐free survival (DFS), and progression‐free survival (PFS) rates after the second surgery. The surgical safety endpoints were postoperative mortality and complications (Clavien‐Dindo classification) within 30 days. Results In total, 67 MPR cases were identified. There were no significant differences in the five‐year OS and DFS between the synchronous MPR group (n = 50) and the propensity score‐matched solitary major pulmonary resection group (n = 250) (5‐year OS 84.5% vs. 69.0%, log rank P = 0.112; DFS 64.4% vs. 58.0%, log rank P = 0.278). The five‐year OS and PFS of the metachronous MPR group (n = 17) were significantly better than those in the non‐surgical control group (n = 19) (5‐year OS 94.1% vs. 50.7%, log rank P = 0.005; 5‐year PFS 53.9% vs. 10.5%, log rank P = 0.020). No postoperative mortality or severe complications occurred in the MPR group. Conclusion The oncological efficacy of MPR is superior to the non‐surgical approach for the management of local regional recurrent or second primary lung cancer, with comparable postoperative mortality and complications.

Inducing DNA damage is known to be one of the mechanisms of cytotoxic chemotherapy agents for cancer such as cisplatin. The endogenous DNA damage response confers chemoresistance to these agents by repairing DNA damage. The initiation and transduction of the DNA damage response (DDR) signaling pathway, which is dependent on the activation of ATM (ataxia-telangiectasia mutated) and ATR (ataxia telangiectasia and Rad3-related), is essential for DNA damage repair, the maintenance of genomic stability and cell survival. Therefore, ATM or ATR inhibition is considered as a promising strategy for sensitizing cancer cells to chemotherapy. This study is aimed to explore the effect of ATR inhibitor on sensitizing ESCC (esophageal squamous cell carcinoma) cells to cisplatin, and whether ATM deficiency could impact the sensitization. We found that 21.5% of ESCC cases had ATM deficiency and that patients with ATR activation after neoadjuvant chemotherapy had worse chemotherapy response and poorer overall survival than that without ATR activation (32 mons vs. >140mons). Then, it was shown that VE-822 inhibited ATR-CHK1 pathway activation, leading to the accumulation of cisplatin-modified DNA. And it inhibited cell proliferation, induced cell cycle arrest in G1 phase and enhanced cell apoptosis. Moreover, VE-822 significantly sensitized ESCC cells to cisplatin, and these two drugs had synergistic effects, especially in ATM-deficient cells, in vitro and in vivo. Our results suggest that ATR inhibition combining with cisplatin is a new strategy for managing patients with ESCC, especially those with ATM-deficiency. However, this is an idea that requires further validation.

BACKGROUND Chemoresistance often develops in esophageal squamous cell carcinoma (ESCC), leading to poor prognosis. HOX genes play a crucial role in embryonic development and cell differentiation. Studies have recently linked HOX with chemoresistance, thus we explored whether HOXA13 is involved in ESCC chemoresistance. METHODS One hundred thirty-one ESCC patients who received neoadjuvant chemotherapy were enrolled. HOXA13 expression was examined by immunohistochemistry. RNA interference was used to knock down the HOXA13 expression in KYSE70 and transfected HOXA13 plasmid to overexpress HOXA13 in KYSE510 cells. We examined half-maximal inhibitory concentration of cisplatin, apoptosis, and epithelial-to-mesenchymal transition (EMT) in ESCC cell lines with different HOXA13 expression levels by cell counting kit-8, flow cytometry, and transwell analysis. RESULTS The median survival of patients with high HOXA13 expression was significantly shorter than those with low expression (P = 0.027). HOXA13 was associated with worse tumor regression grade (P = 0.009). Low HOXA13 expressed cells decreased the half-maximal inhibitory concentration of cisplatin (P

Background The role of postoperative radiotherapy (PORT) in patients with clinical stage III-N2 (cIII-N2) non-small cell lung cancer (NSCLC) treated with induction chemotherapy and surgical resection with persistent ypN2 disease is not well established. Methods We retrospectively reviewed a prospectively maintained database for patients with cIII-N2 NSCLC who underwent induction chemotherapy followed by resection (2004–2016). Exclusion criteria included induction radiotherapy, non–biopsy-confirmed cN2 disease, incomplete resection, ypN0/1, and nonanatomic resection. The primary outcome was locoregional recurrence (LR); secondary outcomes were disease-free survival (DFS), lung cancer–specific death (LCSD), and overall survival (OS). Associations between variables and outcomes were assessed using Fine and Gray competing risk regression for LR/LCSD and Cox proportional hazard models for survival. Results Of the 501 patients identified with cIII-N2 disease, 99 met the inclusion criteria. Median follow-up was 25 months (range, 3-137 months). Sixty-nine patients (70%) received PORT. Sixty (61%) developed a recurrence: 3 (5%) with an initial isolated LR and 57 (95%) with an initial distant recurrence. On multivariable analysis, PORT was not associated with LR (HR, 0.51 [95% CI, 0.22-1.21], p = 0.13). PORT was also not associated with DFS (p = 0.6) or LCSD (p = 0.1). PORT was associated with improved 3-year OS (55% [95% CI, 42%-71%]) versus the no-PORT group (50% [95% CI, 34%-74%]) (p = 0.04). Conclusions PORT is not independently associated with decreased LR or improved DFS/LCSD in this patient population. Given that the predominant failure pattern was distant recurrence, future clinical trials should focus on adjuvant systemic therapies, which may decrease distant recurrences in ypN2 patients.

Non-small cell lung cancer (NSCLC) accounts for 80 % of lung cancers, and lung adenocarcinoma (ADC) is one of the main types of NSCLC. Although there are several studies on the relationship between lung ADC immunohistochemical diagnostic markers (thyroid transcription factor 1 (TTF-1) and Napsin A) and survival, some aspects of those studies could be improved. We examined the significance of the commonly used lung ADC diagnostic markers, including TTF-1, Napsin A, and CK7, in the prognosis of early-stage lung ADC. One hundred and nineteen cases of early-stage lung ADC (N0) were selected from the prospective database of lung cancer (Jan 2000 to Dec 2009). The expression levels of TTF-1, Napsin A, and CK7 in inventoried specimens were analyzed using tissue microarray (TMA) and immunohistochemical (IHC) analysis, and the effect of the expression level of each marker on patients’ survival was examined. The diagnostic sensitivity and specificity of each marker for lung ADC were as follows: TTF-1, 87.0 and 90.1 %; Napsin A, 72.2 and 90.4 %; and CK7, 94.6 and 76.0 %, respectively. Patients with high expression levels of TTF-1 and Napsin A, and high co-expression levels of TTF-1/Napsin A had better survival rates than those with low levels of expression (P

Accurate prediction of treatment response and prognosis before surgery allows prompt therapy adjustment. This study aimed to evaluate the efficacy of computed tomography (CT) signs in predicting treatment response and survival for advanced esophageal squamous cell carcinoma patients who received preoperative chemotherapy. This study retrospectively enrolled 135 consecutive patients with preoperative chemotherapy from September 2005 to December 2011. A logistic regression model was used to evaluate the association between pathologic response and CT signs. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan–Meier method, and a Cox proportional hazards model was constructed to determine associations between CT signs after neoadjuvant chemotherapy and survival outcomes. Logistic regression showed that the significant predictors of a poor response were the total number of lymph nodes (LNs) (>6) at baseline [odds ratio (OR) 5.07; 95 % confidence interval (CI) 1.86–13.81; P = 0.002] and the CT value change rate (≤17 %) (OR 2.35; 95 % CI 1.05–5.23; P = 0.037). In the Cox analyses, the significant predictors of OS were preoperative tumor thickness (>10 mm) [hazard ratio (HR) 2.33; 95 % CI 1.36–4; P = 0.002), total number of LNs (>6) (HR 1.88; 95 % CI 1.12–3.17; P = 0.017), and short diameter of the largest LN (>10 mm) (HR 1.87; 95 % CI 1.07–3.28; P = 0.028), whereas only the short diameter of the largest LN was a significant predictor of DFS (HR 2.36; 95 % CI 1.23–4.54; P = 0.01). CT signs can predict therapeutic efficacy and survival outcomes and provide an opportunity to offer additional treatment options before surgery.

BACKGROUND: Non-small cell lung cancer (NSCLC) accounts for 80% of lung cancers, and lung squamous cell carcinoma (SQCC) is one of the main types. Advances in the treatment of lung SQCC are lacking when compared to lung adenocarcinoma. The main treatment for early-stage SQCC is surgery. However, factors affecting the efficacy of surgical treatments for early-stage lung SQCC remain unclear. In this study, we examined the significance of commonly used lung SQCC diagnostic markers p63, p40, and cytokeratin (CK)5/6 in prognosis. METHODS: Seventy-six cases of early-stage lung SQCC (N0) were obtained from our lung cancer database (January 2000 to December 2009). Tissue microarray and immunohistochemical (IHC) staining were used to detect the expression of p63, p40, and CK5/6. The effect of the expression level of each marker on patients' survival was examined. RESULTS: Sensitivity and specificity of each marker for detecting lung SQCC was 87.0% and 81.0% for p63, 75.9% and 97.9% for p40, and 78.9% and 97.7% for CK5/6. Survival rates of patients with high expression levels of p63 or CK5/6 or both were higher than in patients with low expression levels (P 0.05). Multivariate analysis showed that high levels of p63 expression p63+CK5/6 co-expression were independent prognostic factors for good survival. CONCLUSION: IHC staining detection of p63 and CK5/6 in specimens should be routinely performed in postoperative early-stage lung SQCC patients. Its significance lies not only in differential diagnosis, but also in determining prognosis.

Esophageal squamous cell carcinoma (ESCC), a common disease in China, is mainly treated surgically. We established a prospective database of patients with esophageal cancer between January 2000 and December 2010, including 486 subjects with ESCC who underwent surgical treatment. In this study, we explored the prognostic significance of the expressions of HOXC6 and HOXC8, responsible for embryonic development, by studying the specimens collected from clinical subjects during strict follow-up periods.Immunohistochemistry was used to detect the expressions of HOXC6 and HOXC8 in 274 ESCC subjects including 138 ESCC subjects treated with surgery alone and 136 ESCC subjects treated with neoadjuvant chemotherapy. Survival analysis was performed from the day of surgery to August 2013.The 5-y survival rate of the 274 ESCC subjects was 44.2%, with a median survival time of 44.12 mo. For the 274 ESCC subjects involved in the investigation of HOXC6 and HOXC8 expressions, the median survival time of subjects with high-level expressions of HOXC6 and HOXC8 was shorter than that for subjects with low-level expressions (P = 0.001, P 0.001, respectively). Similar results were obtained from the analysis of the prognostic value of HOXC6 and HOXC8 in the group treated with surgery alone and the group treated with neoadjuvant chemotherapy. Multivariate analysis demonstrated that HOXC6 and HOXC8 expressions were independent prognostic factors in patients with ESCC.The HOXC6 and HOXC8 genes can be used as prognostic markers in patients with ESCC, but prospective studies are still needed to confirm.

Much research effort has been devoted to identifying prognostic factors for esophageal squamous cell carcinoma (ESCC) by immunohistochemistry; however, no conclusive findings have been reached thus far. We hypothesized that certain molecules identified in previous studies might serve as useful prognostic markers for ESCC. Therefore, the aim of the current study was to validate the most relevant markers showing potential for ESCC prognosis in our prospective esophageal cancer database. A literature search was performed using the PubMed database for papers published between 1980 and 2015 using the following key words: 'esophageal cancer,' 'prognosis,' and 'immunohistochemistry.' Literature selection criteria were established to identify the most widely studied markers, and we further validated the selected markers in a cohort from our single-surgeon team, including 153 esophageal cancer patients treated from 2000 to 2010. A total of 1799 articles were identified, 82 of which met the selection criteria. Twelve markers were found to be the most widely studied, and the validation results indicated that only P21, COX-2, and E-cadherin were independent prognostic factors for ESCC patients in this series. The systemic review and cohort validation suggest that P21, COX-2, and E-cadherin are potential prognostic factors for ESCC, paving the way for more targeted prospective validation in the future.

Yang and colleagues report on a multidisciplinary management strategy for marginally operable stage IIIA non-small cell lung cancer (NSCLC) (1). The authors used a very broad definition of “marginally operable,” as tumors with bulky or multistation N2 disease, invasion of a rib or diaphragm, atelectasis, or superior sulcus tumors. From 2006 to 2013, a treatment strategy termed “phased concurrent chemoradiotherapy” (CCRT) was employed, followed by assessment 4 weeks after CCRT to assess operability (Group A, N=16). If the patient was deemed to be inoperable, the patient received more chemotherapy and a boost of up to 30 Gy of radiation (Group B, N=12). The authors then compared these two groups to patients who underwent definitive CCRT (Group C, N=19). Per the authors, the purported rationale for this phased approach in the “marginally operable” patient is “to decrease the toxicities associated with CCRT and to maximize resectability”.

To summarize the mortality of esophagectomy in our series and compare the different mortalities based on 30-day deaths and 90-day deaths postoperatively.A total of 954 patients undergoing esophagectomy by single-surgeon-team between January 2000 and December 2012 from our prospective database were enrolled. The mortalities based on 30-day and 90-day deaths postoperatively were compared, and the causes of deaths within 30 days and 90 days were analyzed.Among all these 954 patients, a total of 20 postoperative deaths(2.1%) were observed: 11 within 30 days(1.1%) and 9 between 30 and 90 days after surgery(1.0%). The reasons for deaths within 30 days were as follows: 3 for respiratory failure related to anastomotic leakage,1 for bleeding after stenting due to anastomotic fistula, 1 for sepsis, 3 for respiratory failure from presenting preoperative respiratory morbidities, 2 for cardiac arrest caused by preoperative heart disorder, and 1 for multiple organ failure caused by early adjuvant chemotoxicity. The reasons for deaths between 30 and 90 days were as follows: 1 for respiratory failure related to anastomotic leakage, 1 for cardiac arrest from preoperative heart disorder, 1 for cerebrovascular accident, 1 for liver failure from liver cirrhosis presenting preoperatively, 1 for renal failure after operation, 1 for tumor progression and 2 for unknown reasons.Since postoperative mortality calculated based on 30 days deaths postoperatively may underestimate the risk of esophagectomy, mortality calculated based on 90 days may be a better option.

It has still been controversial to treat N2-IIIa non-small cell lung cancer (NSCLC) patients by surgery or non-surgery. We retrospectively analysed the survival of 121 stage N2-IIIa NSCLC patients treated with surgery and explored their postoperatively long-term prognostic factors.All of 1,290 patients in Beijing Cancer Hospital underwent resection by single-surgeon-team, among which 121 cases with stage N2-IIIa were enrolled in the study. We retrospectively analysed the impact of gender, age, smoking, perioperative chemotherapy, incision, histological type, vascular tumor emboli, pTstage and tumor size on survival of stage N2-IIIa patients, and compared the survival between patients with single-and multi-station N2 metastasis, and between intraoperatively or postoperatively pathological N2 (IIIa1/a2) and preoperative N2 (IIIa3/a4). Univariate analysis was conducted by Kaplan-Meier curve, and significance test was performed by Log-rank test and Cox regression factor analysis was applicated for multivariate analysis.The 5-yr of all the 121 cases was 43.6%, with a median survival time being 50.3 mo. Univariate analysis showed the 5-year survival rate in patients with single- and multi- station N2 metastasis were 58.3% and 25.5%, respectively (P=0.001), 5-year survival rate in patients with stage IIIa1/a2 and stag IIIa3/a4 were 52.7% and 38.4%, respectively (P=0.020). Multivariate analysis demonstrated that only single station N2 (HR=0.326, 95%CI: 0.186-0.572, P0.001) and IIIa1/a2 (HR=0.494, 95%CI: 0.259-0.941, P=0.032) were independent prognostic factors for stage N2-IIIa lung cancer patients.The prognosis of stage N2-IIIa NSCLC patients with single-station N2 metastasis were better than those with multi-station N2 metastasis. Besides, IIIa1/a2 patients had a better survival compared with stage IIIa3/a4 patients. A multi-disciplinary comprehensive treatment based on surgery may allow patients with high selective stage N2-IIIa NSCLC to obtain a comparatively satisfying long-term survival. .背景与目的 N2-IIIa期非小细胞肺癌（non-small cell lung cancer, NSCLC）手术抑或非手术仍存颇多争议。我们通过回顾性分析121例手术的N2-IIIa期NSCLC患者的生存，探讨N2-IIIa期NSCLC患者术后远期生存的因素。方法 选取北京大学肿瘤医院单医生组肺癌前瞻性数据库2000年1月-2013年6月共1,290例NSCLC手术患者，其中N2-IIIa期NSCLC患者121例。分析性别、年龄、吸烟、围手术期化疗、切口、病理、脉管癌栓、pT分期、肿瘤大小对N2-IIIa期患者生存的影响；比较单站N2与多站N2的生存差异；比较术中或术后病理N2者（IIIa1/a2）与治疗前N2者（IIIa3/a4）的生存差异。单因素分析采用Kaplan-Meier法计算生存，Log-rank检验。多因素分析采用Cox回归分析。结果 全组121例患者5年生存率为43.6%，中位生存时间50.3个月。单因素分析显示单站N2转移与多站N2转移的5年生存率分别为58.3%和25.5%（P=0.001）；IIIa1/a2期者与IIIa3/a4期者5年生存率分别为52.7%和38.4%（P=0.020）。多因素分析显示仅单站N2转移（HR=0.326, 95%CI: 0.186-0.572, P0.001）与IIIa1/a2（HR=0.494, 95%CI: 0.259-0.941, P=0.032）是影响本组N2-IIIa期患者远期生存的独立因素。结论 N2-IIIa期NSCLC中单站N2转移者预后好于多站N2转移者。IIIa1/a2期患者预后好于IIIa3/a4期患者。高选择性N2-IIIa期NSCLC患者采取以外科手术为主的多学科综合治疗可获得较满意的远期生存。.

Background The efficacy of surgery alone for patients with locally advanced esophageal cancer (EC) is still unsatisfactory. Presently, induction therapy followed by surgery is the standard treatment. Preoperative chemotherapy (CT) and chemoradiation (CRT) are proven effective induction therapies; however, few sample studies have addressed these treatments, thus, their superiority remains uncertain. We performed a systemic review and meta analysis to test the hypothesis that induction CRT prior to surgery could improve survival compared with induction CT alone. Methods A comprehensive search of PubMed and the Ovid database for relevant studies comparing EC patients undergoing resection after treatment with induction CT alone or induction CRT was conducted. Hazard ratios (HR) and 95% confidence intervals (95% CI) were extracted from these studies to provide pooled estimates of the effect of induction therapy on overall survival. Results Five studies met the criteria for analysis. Statistical analysis demonstrated a survival benefit of induction CRT compared with induction CT alone (HR0.73, 95% CI 0.61–0.89; P = 0.002). Further analysis showed that induction CRT perioperative mortality and complication rates were higher than for induction CT alone (HR 2.96, 95% CI 1.38–6.37; HR1.6, 95% CI 1.30–1.98; P = 0.01, respectively). Conclusions Published evidence comparing the different efficacies of induction CT and induction CRT is sparse, with few samples of adenocarcinoma. This analysis supports the view that, compared with induction CT, induction CRT could achieve a long-term survival benefit in EC patients.

Background We observed abnormal HOXB7 expression in esophageal squamous cell carcinoma (ESCC) previously. This study was to evaluate the prognostic significance of HOXB7 and reveal the potential mechanism. Methods Immunohistochemistry was used to confirm the abnormal expression of HOXB7 in ESCC. The prognostic significance of HOXB7 expression was analyzed in two independent cohorts. RNAi was used to establish two stable HOXB7-knockdown cell strains. CCK8 assay, cell growth curve assay, colony formation assay, flow cycle analysis and tumorigenicity assay in nude mice were employed to investigate the effect of HOXB7 on proliferation in vitro and in vivo. Results Immunohistochemistry confirmed the abnormal expression of HOXB7 in ESCC compared with paracancerous mucosa (18/23 vs. 9/23, p=0.039). HOXB7 expression was positively correlated with the T stage, lymph node metastasis and TNM stage. The median survival of patients with high HOXB7 expression was significantly shorter than that with low expression (45 months vs. 137 months, p = 0.007 for cohort 1; 19 months vs. 34 months, p = 0.001 for cohort 2). Multivariate survival analysis showed that HOXB7 expression was another independent prognostic factor (HR [95% CI] = 0.573 [0.341–0.963], p = 0.036 for cohort 1; HR [95%CI] = 0.543 [0.350–0.844], p = 0.024 for cohort 2). Experiments in vitro and in vivo showed that after knockdown of HOXB7, the proliferation rate dropped, growth rate descended, colony-formation ability reduced, G1-phase arrest occurred and the tumorigenicity reduced remarkably. Conclusions HOXB7 could promote cancer cell proliferation and might be an independent prognostic factor for patients with ESCC.

Analysis of circulating tumor DNA (ctDNA) is emerging as a powerful tool for guiding targeted therapy and monitoring tumor evolution in patients with non-small cell lung cancer (NSCLC), particularly when fresh tissue biopsy is not available. This study compared the ability of four leading technology platforms to detect epidermal growth factor receptor (EGFR) mutations (L858R, exon 19 deletion, T790M and G719X) in ctDNA from NSCLC patients. The platforms included two amplification refractory mutation systems (cobas-ARMS and ADx-ARMS), a droplet digital polymerase chain reaction platform (ddPCR) and a next-generation sequencing platform (Firefly NGS). Fifteen EGFR mutations across twenty NSCLC patients were identified. We observed superior sensitivity and specificity of cobas-ARMS, ddPCR and Firefly NGS platforms, while ADx-ARMS was only suitable for the qualitative detection of EGFR mutations with allele frequency higher than 1% in plasma samples. We observed high concordance between the plasma and tissue EGFR mutational profiles for three driver mutations that are known targets of the first generation EGFR-TKI therapy (L858R, E19-dels, and G719X). Discrepancies between plasma and tissue EGFR mutational profiling could be attributed to spatial and temporal tumor heterogeneity. This pilot study illustrates the promise of ctDNA analysis in the context of treatment evaluation and drug resistance detection, and results will be validated in follow-up studies. Citation Format: Ting Xu, Xiaozheng Kang, Xiaofang You, Dai Liang, Dequan Tian, Wanpu Yan, Yongbo Yang, Hongchao Xiong, Zhen Liang, Grace Q. Zhao, Shengrong Lin, Ke-Neng Chen, Guobing Xu. Cross-platform comparison of four leading technologies for detecting EGFR mutations in circulating tumor DNA from plasma of patients with non-small cell lung carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2742. doi:10.1158/1538-7445.AM2017-2742

e15525 Background: To (1) evaluate the continuous distribution of tumor regression grade (TRG) in resection specimens after induction chemotherapy for locally advanced esophageal squamous cell carcinoma (ESCC), (2) determine the effects of TRG on survival after esophagectomy, and (3) identify preoperative predictors of TRG. Methods: From June 2001 to October 2012, 212 patients underwent induction chemotherapy followed by esophagectomy for locally advanced ESCC. TRG, assessed as the percentage of residual primary ESCC cells in resection specimens, was classified histologically by pathologists. Random Forest technology was used for data analysis. A nomogram was developed allowing prediction of TRG through use of preoperative clinical factors for patients with clinically locally advanced ESCC who are candidates for treatment with a radical esophagectomy. Results: Twenty-four specimens (11%) had no residual primary cancer (ypT0), 39 (18%) had 1% to 10% residual cancer, 48 (23%) had 11% to 50%, 101 (48%) had more than 50%. Survival was worse with increasing residual primary ESCC, plateauing at 50%. Poorer TRG was associated with worse 3-year overall survival. Better pathologic grade (G), larger number of pack year smoking, fewer cycles of induction chemotherapy, lower level of creatinine, younger age, greater tumor length and clinical T stage were associated with poorer TRG. Conclusions: Better TRG in response to preoperative chemotherapy is associated with a linear increase in survival after esophagectomy for locally advanced ESCC. A nomogram has been developed that can be used to predict TRG. Therefore, for patients with poorer TRG, the role of adjuvant therapy needs to be further assessed in an attempt to improve survival.